Future challenges of stroke treatment

Posterior circulation stroke accounts for approximately 20% of all ischaemic strokes. Acute basilar artery occlusion (BAO) is one of the most severe conditions, it is associated with death or major disability in more than three quarters of the cases, and its optimal management remains unestablished. Currently, the treatment is based primarily upon consensus, the clinical practice varies widely, and the actual benefit of mechanical thrombectomy has to be fully estimated. Although the recent years have profoundly revolutionized and improved the stroke care, many questions still remain unanswered and will represent the challenges of the next future

Model-independent Bounds on the Standard Model Effective Theory from Flavour Physics

Meson-antimeson mixing provides the most stringent constraints on baryon- and lepton-number conserving New Physics, probing scales higher than $10^5$ TeV. In the context of the effective theory of weak interactions, these constraints translate into severe bounds on the coefficients of $\Delta F=2$ operators. Generalizing to the effective theory invariant under the Standard Model gauge group, valid above the electroweak scale, the bounds from $\Delta F=2$ processes also affect $\Delta F=1$ and even $\Delta F=0$ operators, due to log-enhanced radiative corrections induced by Yukawa couplings. We systematically analyze the effect of the renormalization group evolution above the electroweak scale and provide for the first time the full set of constraints on all relevant dimension-six operators.Comment: 8 pages, 8 tables. Table of DF=2 bounds on weak Hamiltonian added. Revised version published in Physics Letters

Medical Implications of the Relationships among Protein Denaturation, Necrosis and Inflammation: An Intriguing Story

This story deals with the role of protein denaturation in inflammation. The starting point was the description of the necrotizing action of inflammatory proteins, followed by the discovery of the antidenaturant action of NSAIDs (nonsteroidal anti-inflammatory drugs). Hence, the idea is that the antidenaturant action accounted for the action of NSAIDs. This hypothesis was dropped following the discovery of the antiprostaglandin action of NSAIDs, which shifted the focus to the arachidonic acid cascade. It was revived by assuming that protein denaturation is a process in its own, suitable for separate medical treatment. This approach led to bendazac and bindarit, the first selective antidenaturant drugs. This experience shows that protein denaturation has two main pathological sequelae. The first concerns the so-called primary (innate) inflammation. The second sequela concerns the so-called secondary (acquired) inflammation. Natural antidenaturant agents represent a promising alternative to the synthetics bendazac and bindarit. Within this framework, tendinitis finds a separate but significant place

Cortical laminar necrosis following myocardial infarction

The cortical laminar necrosis (CLN) is a permanent injury characterized by the selective delayed necrosis of the cerebral cortex, mainly of the third layer, and usually greater in the depths and sides of the sulci than over the crest of the gyri. The damage involves all cellular components – either neurons, glia cells and blood vessels – and results in a focal cortical band of pan-necrosis detectable in late sub-acute or chronic stages of reduced energy supply to the brain. The CLN has been described in different conditions as hypoxia, hypoglycemia and status epilepticus. At brain CT or MR scans it appears with pathognomonic highly hyperdense or T1-hyperintense lesions following the gyral anatomy of the cerebral cortex. We reported a case of CLN associated to myocardial infarct and discussed the underlying mechanisms

B→K∗ℓ+ℓ−B\to K^* \ell^+ \ell^- decays at large recoil in the Standard Model: a theoretical reappraisal

We critically reassess the theoretical uncertainties in the Standard Model calculation of the $B \to K^* \ell^+ \ell^-$ observables, focusing on the low $q^2$ region. We point out that even optimized observables are affected by sizable uncertainties, since hadronic contributions generated by current-current operators with charm are difficult to estimate, especially for $q^2 \sim 4 m_c^2\simeq 6.8$ GeV$^2$. We perform a detailed numerical analysis and present both predictions and results from the fit obtained using most recent data. We find that non-factorizable power corrections of the expected order of magnitude are sufficient to give a good description of current experimental data within the Standard Model. We discuss in detail the $q^2$ dependence of the corrections and their possible interpretation as shifts of the Standard Model Wilson coefficients.Comment: 33 pages, 7 figures, 11 tables. v2: fixed numerical error in S4 and typos; added discussion of the impact of future measurements; conclusions unchange

On Flavourful Easter eggs for New Physics hunger and Lepton Flavour Universality violation

Within the standard approach of effective field theory of weak interactions for $\Delta B = 1$ transitions, we look for possibly unexpected subtle New Physics effects, here dubbed "flavourful Easter eggs". We perform a Bayesian global fit using the publicly available HEPfit package, taking into account state-of-the-art experimental information concerning these processes, including the suggestive measurements from LHCb of $R_{K}$ and $R_{K^{*}}$, the latter available only very recently. We parametrize New Physics contributions to $b \to s$ transitions in terms of shifts of Wilson coefficients of the electromagnetic dipole and semi-leptonic operators, assuming CP-conserving effects, but allowing in general for violation of lepton flavour universality. We show how optimistic/conservative hadronic estimates can impact quantitatively the size of New Physics extracted from the fit. With a conservative approach to hadronic uncertainties we find nonzero New Physics contributions to Wilson coefficients at the level of $\sim 3\sigma$, depending on the model chosen. Furthermore, given the interplay between hadronic contributions and New Physics effects in the leptonic vector current, a scenario with nonstandard leptonic axial currents is comparable to the more widely advocated one with New Physics in the leptonic vector current.Comment: 27 pages, 6 figures and 5 tables. v2: numerical results and plots replaced with higher statistics MC runs, references added. v3: final version to appear in EPJ

Lacosamide during pregnancy and breastfeeding

Background The epilepsy treatment during pregnancy represents a balance between teratogenic hazard and seizure control. The aim of the study was to evaluate the safety and efficacy of lacosamide (LCS) during pregnancy and breastfeeding. Methods Patients referred to our Epilepsy Center for pregnancy planning who became pregnant while taking LCS were prospectively followed-up. Data on seizure frequency, side effects, pregnancy course, delivery and breastfeeding, birth outcome, congenital malformation and development of newborns were collected. Results Three cases of maternal exposure to LCS were reported. Treatment with LCS was continued throughout pregnancy and breastfeeding at a median daily dose of 400mg. Lacosamide was used as monotherapy in two patients and as add-on treatment in one woman. Seizure frequency did not change throughout pregnancy and two subjects remained seizure free. The median gestational age at delivery was 39 weeks. The median Apgar scores at 1 and 5min were 9 and 10, respectively; no major or minor congenital malformations were observed in the offspring. Normal developmental milestone were reached by all new-borns. Conclusions Worldwide pregnancy registries have provided consistent and increasing information about the efficacy and safety of the older antiepileptic drugs during gestation, while data are lacking for many of the newer generations. These cases could suggest a good level of efficacy and safety for LCS throughout pregnancy and breastfeeding and argue against teratogenic or toxic potentialities

Lacosamide monotherapy for partial onset seizures

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